Electrokinetic chromatography neutral analyte

Razak, J. L., Cutak, B. J., Larive, C. K., Lunte, C. E. Correlation of the capadty factor in vesicular electrokinetic chromatography with the octanobwater partition coefficient for charged and neutral analytes. Pharm. Res. 2001, 18, 104-111. 

P. Bocek, Sweeping of Neutral Analytes in Electrokinetic Chromatography with High-Salt-Containing Matrixes, Anal. Chem. 2000, 72, 1934. 

Many pharmaceutical preparations contain multiple components with a wide array of physico-chemical properties. Although CZE is a very effective means of separation for ionic species, an additional selectivity factor is required to discriminate neutral analytes in CE. Terabe first introduced the concept of micellar electrokinetic capillary chromatography (MEKC) in which ionic surfactants were included in the running buffer at a concentration above the critical micelle concentration (CMC) [17], Micelles, which have hydrophobic interiors and anionic exteriors, serve as a pseudostation-ary phase, which is pumped electrophoretically. Separations are based on the differential association of analytes with the micelle. Interactions between the analyte and micelles may be due to any one or a combination of the following electrostatic interactions, hydrogen bonding, and/or hydro-phobic interactions. The applicability of MEKC is limited in some cases to small molecules and peptides due to the physical size of macromolecules... 

Micellar electrokinetic chromatography has been proven to be a highly efficient separation method for neutral analytes (63,67,68), neutral and charged compounds (69-72), and ionized compounds (67,73) including PTH-amino acids (18). 

As shown in Eq. (2) together with the chiral recognition Kk + Kg), the other necessary requirement for enantioseparations in CE is a mobility difference between the free and the complexed analyte fXf - fjL, 0). Otherwise, it will be impossible to transfer a chiral recognition into a chiral separation. This requirement does not hold when neutral analytes are analyzed with neutral chiral selectors. In such a case, an additional buffer component is required that will assist in generating a difference between the mobilities of an analyte in its free and complexed forms with a chiral selector. This is achieved by an achiral micellar phase in cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) [9]. However, a charged CD or a chiral micellar phase can combine the... 

Micellar electrokinetic capillary chromatography (MEKC or MECC) is the mode employed for separating of neutral analytes by CE. In CZE, neutral molecules migrate together as one unresolved peak. MEKC can also improve resolution for cation and anion separations too. It normally utilises a bare fused silica capillary. The electrolyte contains micelles which have a polar, negatively charged exterior and a nonpolar interior. The... 

A considerable number of CE separation methods exist for a wide variety of analytes. However, nitrosamines separation and determination by CE requires additional development for its practical use. " " For the separation of hydrophilic, low molecular weight, neutral, and polar compounds such as nitrosamines, it is necessary to develop CE techniques for enhancing the selectivity. The main reason is that these compounds do not interact strongly with the commonly used surfactants (e.g., sodium dodecyl sulfate, SDS) or other buffer modifiers such as cyclodextrins in electrokinetic chromatography. The separation depends on several factors which must be optimized to reach... 

The general resolution equation for two neutral analytes with similar retention factors in micellar electrokinetic chromatography, is similar to the relationship for chromatography (section 1.6) with an additional term that arises from the limited migration time window [11,12,166,177,178]. 

Neutral cyclodextrins are also used in micellar electrokinetic chromatography with achiral surfactants to modify their enantioselectivity, particularly for the separation of hydrophobic analytes [53,55,185-187]. Enantioselectivity in this case results from differences in the distribution of enantiomers between the micellar pseudostation-ary phase and the cyclodextrin, as well as from the different migration velocities of the cyclodextrin and micelles. Neutral enantiomers can be separated based on differences in their equilibrium constants between the electrolyte solution and a charged chiral surfactant micellar phase, if the micelle has a different electrophoretic mobility to the free enantiomers. Suitable chiral surfactants include the bile salts (section 8.3.3), long alkyl-chain amino acid derivatives (e.g. sodium N-dodecanoyl-... 

Capillary electrophoresis has a wide applicability. High molecular weight compounds such as proteins, nucleic acids and oligosaccharides can be separated as well as smaller biomolecules such as peptides and amino acids. CE is not restricted to charged analytes. Neutral molecules can be separated from each other by employing a variation of CE called micellar electrokinetic chromatography (MEKC). This is frequently used for the separation of chiral drugs in pharmaceutical research. 

Separation in Micellar Electrokinetic Chromatography (MEKC) is based on partitioning of the analyte molecules between the aqueous run buffer and the core of micelles, which are contained in the run buffer. The technique is essentially a hybrid between CE and liquid chromatography (LC). The run buffer and micelles are moved through the capillary by an applied electric field. The analytes are dragged with the bulk solution. Similar to LC, the analytes partition between two phases, in this case two mobile phases, the hydrophilic run buffer and the hydrophobic micelles. Unlike other electrophoresis modes, MEKC can distinguish between different neutral compounds according to their hydrophobicity. 

Quirino, J.R. and Terabe, S., On-line concentration of neutral analytes for micellar electrokinetic chromatography. 3. Stacking with reverse migrating micelles. Anal. Chem., 70,149, 1998. 

Palmer, J., Munro, N.J., and Landers, J.R, A universal concept for stacking neutral analytes in micellar electrokinetic chromatography, AnaZ. Chem., 71, 1679, 1999. 

Tesaf ova et al. [87] used a modified version of SIMUL, which they called SIMULMIC to simulate the separation of neutral analytes in a system with a neutral cyclodextrin and anionic micelles. A number of systems were examined in which various combinations of the inlet and outlet vials and the capillary itself were filled with cyclodextrin. Simulation results were used to examine the micellar/cyclodextrin boundary at various times and concentrations although no simulation results for a chiral separation were reported. To the best of our knowledge, this is the only dynamic simulation of an electrokinetic chromatography (EKC) separation to date. 

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